Abstract
Background: Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. Methods: A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. Results: All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh the health benefits of testing, resulting in overall QALY loss. Conclusions: Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is predicted to be a cost-effective use of limited financial resources in England and Wales. Research is recommended into the cost-effectiveness of reflex testing for Lynch syndrome in other associated cancers and into the impact of prophylactic H-BSO on HRQoL.
| Original language | English |
|---|---|
| Article number | 313 |
| Journal | BMC Cancer |
| Volume | 15 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 25 Apr 2015 |
Bibliographical note
Funding Information:We would like to thank: Dr Carole Brewer, Mr Ian Daniels and Mr John Renninson (all of Royal Devon and Exeter NHS Trust) for sharing their clinical expertise; Dr Mercy Mvundura (previously of Centers for Disease Control and Prevention) and Dr Scott Grosse (Centers for Disease Control) for providing us with a copy of their model for the cost-effectiveness of genetic testing for Lynch syndrome; Dr Mark Arends (Dept. of Pathology, University of Cambridge), Professor Mary Porteous (University of Edinburgh and SE Scotland Genetics Service), Dr Lorraine Cowley (Institute of Genetic Medicine, Newcastle University), Dr Munaza Ahmed (Wessex Clinical Genetics Service), and Mr Michael Gandy (UCL-Advanced Diagnostics, University College London) for their assistance in parameterising our health economic model; Associate Professor Rob Anderson and Dr Ruben Mujica Mota (both of University of Exeter) for their contributions to the project; and, Sue Whiffin and Jenny Lowe for their administrative support throughout the project. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 10/28/01) and was published in full in the NIHR Health Technology Assessment journal [44] after submission of this article. Further information available at: http://www.nets.nihr.ac.uk/projects/hta/102801 This report presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA programme of the Department of Health.
Publisher Copyright:
© 2015 Snowsill et al.; licensee BioMed Central.
Keywords
- "Colorectal neoplasms, hereditary nonpolyposis" [MeSH]
- "Models, economic" [MeSH]
- Cost-utility analysis
- Lynch syndrome
